The programmed cell death protein 1 (PD-1) signaling axis is among the most important therapeutic targets in modern oncology. Aurigene Discovery Technologies Ltd. (Aurigene) has patented a series of peptidomimetic small molecules derived from the PD-1 protein sequence for use in targeting the interaction between PD-1 and its ligand, PD-L1. We evaluated three of Aurigene's most potent compounds in SPR binding assays. Our results showed that these compounds each of which is known to be potently effective in a splenocyte recovery assaydo not directly inhibit the PD-1/PD-L1 interaction nor do they appear to bind to either of the constituent proteins, indicating that another mechanism is at play. As a result of these studies and upon consideration of structural features within the PD-1/PD-L1 complex, we hypothesize that the Aurigene molecules may interact with a currently unknown protein capable of regulating the PD-1 axis.

Herein, we report a new one-pot sequential method for SO 2 F 2 -mediated nucleophilic acyl substitution reactions starting from carboxylic acids. A mechanistic study revealed that SO 2 F 2mediated acid activation proceeds via the anhydride, which is then converted to the corresponding acyl fluoride. Tetrabutylammonium chloride or bromide accelerate the formation of acyl fluoride. Optimized halide-accelerated conditions were used to synthesize acyl fluorides in 30−80% yields, and esters, amides, and thioesters in 72−96% yields without reoptimization for each nucleophile.

Herein, we report a new method for the one-pot synthesis of 1,1-dihydrofluoroalkyl sulfides by bubbling sulfuryl fluoride (SO2F2) through a solution of the corresponding alcohol and thiol.

Thionyl fluoride (SOF 2 ) is an underutilized reagent that is yet to be extensively studied for its synthetic applications. We previously reported that it is a powerful reagent for both the rapid syntheses of acyl fluorides and for one-pot peptide couplings, but the full scope of these nucleophilic acyl substitutions had not been explored. Herein, we report one-pot thionyl fluoridemediated syntheses of peptides and amides (35 examples, 45− 99% yields) that were not explored in our previous study. The scope of thionyl fluoride-mediated nucleophilic acyl substitutions was also expanded to encompass esters (24 examples, 64−99% yields) and thioesters (11 examples, 24−96% yields). In addition, we demonstrate that the scope of thionyl fluoride-mediated onepot reactions can be extended beyond nucleophilic acyl substitutions to mild reductions of carboxylic acids using NaBH 4 (13 examples, 33−80% yields).